Pituitary disorders such as growth hormone deficiency (GHD), also referred to as Somatotropin Deficiency Syndrome, effect the production and secretion of growth hormone often resulting in short stature and other physical ailments. GHD results in lower levels of endogenous growth hormone, which causes numerous adverse affects on body processes. Growth hormone is critical to tissue growth, and is known to stimulate the growth of such tissue as skeletal, skeletal muscle and organ. Human growth hormone has also been implicated in the metabolism of fat, carbohydrates, proteins and minerals such as potassium and phosphorus.
Human growth hormone (hGH) is a naturally occurring human protein secreted by the pituitary gland which consists of 191 amino acids and has a molecular weight of about 22,000 daltons. hGH may isolated from in its natural form from the pituitary gland of human cadavers, or may be produced recombinantly known genetic engineering techniques. Recombinant production of hGH can yield a variety of hGH species, including a 191 amino acid native species (commonly known as Somatropin), as described for example in U.S. Pat. Nos. 4,670,393, 5,424,199, 5,633,352 and 5,795,745 (the disclosures of which are hereby incorporated by reference) or a 192 amino acid species, met-hGH, having N-terminal methionine (met) (commonly known as Somatrem), such as that described in U.S. Pat. No. 4,658,021, which is hereby incorporated by reference.
Recombinant hGH (both the 191 and 192 amino acid species) has been approved by the FDA for a number of treatments, including the treatment of children and adults suffering from GHD, and the treatment of wasting in individuals suffering from AIDS. One example of approved hGH is Nutropin®, commercially available from Genentech (South San Francisco, Calif.) which consists of 191 amino acids and has been approved for the treatment of GHD, Turner Syndrome and chronic renal failure in children and for the treatment of adults suffering from GHD. Currently, all FDA approved hGH compositions are administered subcutaneously by injection, three times a week or once daily in order to maintain suitable serum levels of hGH.
Buccal delivery is a more preferable method of administering drugs and offers several advantages over subcutaneous injection. Typically, a buccal dosage form is placed in the buccal cavity between the gum and the cheek, where it dissolves in the patient's saliva, releasing the drug into the buccal cavity in close proximity to the capillary bed of the oral mucosa. The drug then enters the blood in the capillary bed by diffusion through the mucosal tissue and is distributed in the bloodstream to the rest of the body.
Buccal administration is less invasive and results in greater patient compliance compared to subcutaneous injection. Furthermore, unlike oral administration, buccal administration avoids the possibility that the drug will be destroyed in the gastrointestinal tract before it can be absorbed, and eliminates first-pass inactivation in the liver after absorption.
Therefore, there is a need for a human growth hormone formulation which can be buccally administered.